Molecular Mechanisms of Cytokinesis

项目摘要 胞质分裂是细胞分裂中的一个重要步骤，在此过程中，新分离的基因组、细胞质和 细胞器从母细胞分裂成两个子细胞。胞质分裂中的关键事件是什么 协调仍然在很大程度上是未知的，因为每个事件和基因的时空分辨率很差 冗余性。我们研究的长期目标是阐明细胞质分裂的分子机制。这个 本应用的目的是研究肌动球蛋白收缩-环收缩的协调性，血浆-肌球蛋白-肌动球蛋白-环收缩、血浆-肌球蛋白和肌动球蛋白-肌球蛋白的相互作用。 胞质分裂过程中的膜沉积和胞外隔膜的形成。裂变型酵母 庞氏裂殖酵母是这些研究的良好模型系统，因为它在遗传上是易驯化的， 具有促进基因打靶的有效同源重组，并使用不同的 时间和空间路径。 之前关于分裂酵母胞质分裂的研究和我们坚实的初步数据导致了我们的中心假设 收缩环收缩通过小泡引导质膜沉积和隔膜形成 胞质分裂过程中的运输途径。我们将通过调查三个具体目标来验证这一假设：我们将 描述1)引起收缩环收缩，2)配位环收缩的分子机制 和质膜沉积；3)协调环状收缩和隔膜形成。我们将聘用 相互补充的方法，包括遗传学、高时空的定量显微成像 这些研究中的分辨率、生物化学和数学建模。 我们将结合创新的方法和假设来调查涉及的三个具体目标 细胞质分裂最保守的方面。四种新蛋白Rng13、Rng14、Rng15和Rng15的功能研究 RNG16将在关键的细胞质分裂事件之间提供分子联系。这些拟议的研究具有重要意义 因为它们将在三个重要方面促进我们对细胞质分裂的理解：a)阐明基本的 关键肌动蛋白结合蛋白在收缩环收缩中的原理和作用；b)转移电流 关于胞质分裂过程中小泡在哪里以及如何被束缚的范例；以及c)阐明葡聚糖合成酶是如何 在分裂部位，协调环收缩和隔膜的形成，以实现细胞质分裂的成功。敏锐的眼光 控制胞质分裂关键事件正确完成和协调的分子机制 模型系统是理解人类细胞中更复杂但相似的过程的关键一步。

Project Summary Cytokinesis is an essential step in cell division during which the newly separated genomes, cytoplasm, and organelles are partitioned from a mother cell into two daughter cells. How key events in cytokinesis are coordinated remains largely unknown because of the poor spatiotemporal resolution of each event and genetic redundancy. The long-term goal of our research is to elucidate the molecular mechanisms of cytokinesis. The objective of this application is to investigate the coordination of actomyosin contractile-ring constriction, plasma- membrane deposition, and extracellular septum formation during cytokinesis. The fission yeast Schizosaccharomyces pombe is a favorable model system for these studies because it is genetically tractable, has efficient homologous recombination facilitating gene targeting, and carries out cytokinesis using distinct temporal and spatial pathways. Previous studies on fission yeast cytokinesis and our solid preliminary data led to our central hypothesis that contractile-ring constriction guides plasma-membrane deposition and septum formation via vesicle trafficking pathways during cytokinesis. We will test this hypothesis by investigating three specific aims: we will characterize the molecular mechanisms that 1) cause contractile-ring constriction, 2) coordinate ring constriction and plasma-membrane deposition, and 3) coordinate ring constriction and septum formation. We will employ complementary approaches including genetics, quantitative microscopic imaging with high spatiotemporal resolution, biochemistry, and mathematical modeling in these studies. We will combine innovative approaches and hypotheses to investigate the three specific aims involving the most conserved aspects of cytokinesis. Our study on roles of four novel proteins Rng13, Rng14, Rng15, and Rng16 will provide molecular links among key cytokinesis events. These proposed studies are significant because they will advance our understanding of cytokinesis in three important ways: a) elucidating the basic principles and contributions of key actin-binding proteins in contractile-ring constriction; b) shifting the current paradigms on where and how vesicles are tethered during cytokinesis; and c) elucidating how glucan synthases at the division site coordinate ring constriction and septum formation for successful cytokinesis. Discerning molecular mechanisms that control proper completion and coordination of key events of cytokinesis in a simple model system is a critical step towards understanding more complicated but similar processes in human cells.